The goal of this project is to determine the mechanism of nutritional programming of bile acid metabolism by breast-feeding vs. formula-feeding and the relationship to thyroid hormone levels. The specific aims are to test the hypotheses that: 1) breast-feeding vs. formula-feeding differentially programs bile acid metabolism in adult baboons; and 2) nutritional programming of thyroxine (T4) and trilodothyronine (T3) concentrations mediates the programming of variables of bile acid formation. Results from our preliminary studies and from those of other groups of investigators have shown that breast-feeding vs. formula-feeding differentially programs lipoprotein concentrations, bile acid synthesis, and atherogenesis in baboons and humans. The proposed studies will identify the specific genes in bile acid metabolism that are programmed by early nutrition and the potential role of thyroid hormones. Expression of genes may be affected by multiple controls, including DNA methylation, transcription factors, or gene structure. The proposed studies will identify the specific genes in bile acid metabolism that are programmed by early nutrition and the potential role of thyroid hormones. Expression of genes may be affected by multiple controls, including DNA methylation, transcription factors, or gene structure. Identification of the genes affected by early diet in this study will provide a basis for future studies on the molecular mechanisms of nutritional programming.